1. Technical Field
The present invention relates to a protein effective in promoting osteogenic differentiation and vascularization, and more specifically, to a peptide exhibiting the activities of promoting osteogenic differentiation or vascularization, and a use thereof.
2. Background Art
Bone decrease is greatly influenced by the change in bone mass. The major factors that affect the change in bone mass include genetic factors, nutrients intake, hormonal change, exercise, and difference in lifestyle, etc. Recently, aging, lack of exercise, low-calcium diet, menopause, ovariectomy, etc., have been known to cause the decrease in bone mass and thereby induce osteoporosis.
Osteoporosis is a disease in which the bones become very weak along with the progress of the symptoms that calcareous deposit in bone tissue decreases, bone density becomes low and medullary cavity becomes wide, thereby easily causing the occurrence of bone-related diseases such as bone fracture even with a slight shock.
Although there is an individual difference, the bone resorption level is lower in black people than in white people and thus black people have higher bone mass. Generally, bone mass reaches the highest level at age between 14 and 18 and decreases about 1% per year at old ages. In particular, bone decrease continuously occurs in women since age 30 and at menopause bone decrease proceeds rapidly due to hormonal change. That is, once women reach menopause they experience a rapid decrease in estrogen level, and in particular, B-lymphocytes are produced in large quantity and thus pre-B cells are accumulated in bone marrow. As a result, the amount of IL-6 increases and thus the activity of osteoclasts increases thereby decreasing bone mass.
Accordingly, although there is a difference in its degree, aged people, especially post-menopausal women, cannot avoid osteoporosis, and in advanced countries with aging population, there is a growing interest in osteoporosis and therapeutic agents thereof.
Additionally, bone-related diseases also include osteoarthritis, bone loss diseases, etc., in addition to osteoporosis. Osteoarthritis is a disease in which a local degenerative change occurs as the cartilage of the joint becomes damaged, and also called degenerative arthritis. There are two main reasons for the occurrence of osteoarthritis, i.e., when joint tissue is damaged due to an overload on the joint although the cartilage or bone of the joint is normal, or when the cartilage or bone is weak although the load on the joint is normal.
Bone loss diseases may occur in many areas of the body, and major reasons of the bone loss diseases may include acute trauma accompanying bone tissue loss, acute trauma accompanying bone loss due to tissue removal during surgery, chronic infection accompanying bone resection, chronic nonunion accompanying segmental bone loss, etc.
There is established a global market associated with the treatment of bone diseases worth of at least about 130 billion US dollars and the size of the market is expected to continue to grow further in the future, and thus global research institutes and pharmaceutical companies have been investing much on the development of therapeutic agents for the treatment of bone diseases.
In particular, in the case of osteoporosis, for example, examples of osteoporosis treatments include androgenic anabolic steroids, calcium preparations, phosphates, fluorine preparations, ipriflavone, vitamin D3, etc. Merck & Co., Inc. (USA) developed aminobisphosphonate in 1953, Lilly Co. (USA) developed raloxifene, which serves as a selective estrogen receptor modulator (SERM), as therapeutic agents for treating osteoporosis.
Meanwhile, estrogen, which is a bone resorption inhibitor, is most widely used as a treatment for osteoporosis. However, a regular use of estrogen can increase the incidence rate of endometrial cancer and breast cancer, and can cause thrombosis, cholelithiasis, hypertension, edema, mastalgia, etc. The follow-up study on post-menopausal women, who were simultaneously administered with estrogen and progesterone, revealed a high incidence rate of breast cancer, stroke, pulmonary embolism, etc.
In addition, bisphosphonate preparations (alendronate and etidronate), vitamin D preparations, calcitonin preparations, calcium preparations, etc., are used as therapeutic agents for osteoporosis. However, these preparations have problems in that bisphosphonate preparations have a low absorption rate, a complicated administration method, causes esophagitis; vitamin D preparations are expensive and their effects have not been confirmed; calcitonin preparations are expensive and have a difficult method of administration; and calcium preparations have few adverse effects but they are effective for prevention rather than treatment of osteoporosis. Furthermore, osteoporosis cannot be treated by short-term administration of drugs but a long-term administration is essential. Accordingly, there is a need for the development of a novel material with excellent effect to replace the existing therapeutic materials without having the above adverse effects.
At present, for the bone morphogenetic activity, bone morphogenetic proteins (BMP), which belong to transforming growth factor (TGF)-β superfamily, have been reported (Science 150, 893-897, 1965; Science 242; 1528-1534, 1988). Known BMP species are from BMP-1 to BMP-14. Among them, BMP-2 to BMP-14 are known to exhibit bone morphogenetic activity. BMP-2 to BMP-14 are thought to be effective for the therapeutic treatment of various bone functional disorders and bone diseases but they are present in trace amounts in nature.
Accordingly, for obtaining BMP-2 to BMP-14, which are used for the above treatment, in large amount to make them affordable, the preparation of recombinant proteins are necessary. The preparation of recombinant proteins, in general, requires a higher expense compared to low molecular weight compounds. On the other hand, due to the proteinaceous characteristics, the recombinant proteins have many restrictions as pharmaceutical drugs from the aspects of physical properties and administration. Under these circumstances, the present inventors had previously developed Bone Peptide Protein 1 (BFP 1), which consists of 15 amino acids, as a low molecular weight organic compound having the same activity as that of BMP proteins.